Generally, most of the peptide pharmaceutical products such as hormones and cytokines, antibody pharmaceutical products, and nucleic acid pharmaceutical products such as siRNA and DNA plasmids are water-soluble compounds of high molecular weight. They have extremely low epithelial permeability and cell membrane permeability. Meanwhile, in many cases, the target molecule (site of action) for these physiologically active substances is present in the cell membrane or in the cells, and the development of pharmaceutical products with these physiologically active substances requires the development of a technique (system) for delivering these physiologically active substances into the target cells. Despite the fact that various drug delivery systems (DDS) have been developed until now, there is no report regarding a system for delivering these physiologically active substances specifically to the target tissues, particularly into the target cells by a means other than injection. This is deemed to be attributable to the fact that development of multifunctional DDS combining both the function of delivering drugs into the body by a means other than injection and the function of delivering drugs specifically to the target site is extremely difficult. Particularly, while the oral route is an easy drug administration route, there are many obstacles in drug delivery.
So far, the present inventors have continued their research on a system for delivering a nucleic acid for suppressing the expression of the target gene using endogenous chylomicrons, and the like. For example, Patent Document 1 describes an agent for suppressing a target gene expression, comprising nucleic acids for suppressing the target gene expression, wherein an introduction substance into chylomicron or chylomicron remnant is bound to the nucleic acids, and wherein the agent is administered to a vertebrate under a condition in which the production of an endogenous chylomicron has been induced in the vertebrate. However, the above agent for suppressing a target gene expression was supposed to be administered by injection such as intravenous injection as the main administration route.
Many of the medically important drugs are administered by injection due to poor absorption through the digestive tract. However, injection therapy imposes mental as well as physical pain on patients, and moreover, the possibility of induction of allergic reactions and tissue damage in the administration site is pointed out. In view of the foregoing, a novel dosage form alternative to an injection agent is demanded, and recently, development of orally or rectally administered agents of poorly absorbable drugs has been attempted.
For example, Non Patent Document 1 describes the possibility of utilization of, as an absorption enhancer for improving the intestinal permeability of poorly absorbable drugs, capric acid, oleic acid, linoleic acid, and their fatty acids such as monoglycerides; sugar esters of fatty acid; glycerol esters of fatty acids; chelating agents such as EDTA and citric acid; and surfactants such as sodium lauryl sulfate. Also, Non-Patent Document 2, which was written by the present inventors, describes that long-chain unsaturated fatty acid and medium-chain fatty acid are excellent absorption enhancers, and a mixed micelle of long-chain unsaturated fatty acid and HCO-60 (nonionic detergent) is particularly excellent.